ABSTRACT
SUMMARY: Osteoarthritis (OA) caused by ageing joints or as a secondary complication of diabetes is a common health problem. We sought to develop an animal model of OA induced by a combination of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA) and streptozotocin (STZ), the agent that induces diabetes mellitus. We then hypothesized that the extent of damages to the knee joint induced by this model can be greater than OA induced by either MIA or STZ. Rats were either injected with MIA (model 1) or STZ (model 2) or both agents (model 3). After 8 weeks, harvested tissues from the knee joint of these groups were examined using scanning and transmission electron microscopy. In addition, blood samples were assayed for tumor necrosis factor alpha (TNF-α) and interleukin -6 (IL-6) that are known to be modulated in OA and diabetes. Compared to control group, substantial damages to the articular cartilage of the knee joint were observed in the three models with the severest in model 3. In addition, rats in model 3 showed significant (P<0.0001) increase in TNF-α and IL-6 compared to model 1 and 2. Thus, we have developed a new model of knee OA in rats that mimics a type of OA that is common among elderly people who have both, "ageing" joints and diabetes.
RESUMEN: La osteoartritis (OA) es un problema generalizado de salud a causa de un envejecimiento de las articulaciones, o bien de una complicación secundaria de la diabetes. El objetivo de este estudio fue desarrollar un modelo animal de OA inducido por una combinación dos drogas, un inhibidor de los condrocitos glucolíticos, el mono-iodoacetato (MIA), y la estreptozotocina (STZ), agente que induce la diabetes mellitus. Se consideró como hipótesis que el alcance de los daños a la articulación de la rodilla inducida por este modelo puede ser mayor que la OA inducida por MIA o STZ. Las ratas fueron inyectadas con MIA (grupo 1) o STZ (grupo 2) o ambos agentes (grupo 3). Se extrajeron muestras de la articulación de la rodilla de estos grupos al término de 8 semanas, y se examinaron mediante microscopía electrónica de barrido y de transmisión. Además, se analizaron muestras de sangre para el factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6), que están moduladas en OA y en la diabetes. En comparación con el grupo control, se observaron daños sustanciales en el cartílago articular de la articulación de la rodilla en los tres modelos, encontrándose los daños más severos en el grupo 3. Además, las ratas del grupo 3 mostraron un aumento significativo (P <0,0001) de los niveles de TNF-α e IL- 6, en comparación con los grupos 1 y 2. Hemos desarrollado un nuevo modelo de OA de rodilla en ratas que imita un tipo de OA el cual, además de la diabetes, es común entre las personas mayores con un nivel importante de daño en las articulaciones.
Subject(s)
Animals , Male , Rats , Streptozocin/toxicity , Osteoarthritis, Knee/chemically induced , Iodoacetic Acid/toxicity , Microscopy, Electron , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Cartilage, Articular/ultrastructure , Rats, Sprague-Dawley , Osteoarthritis, Knee/pathology , Diabetes Mellitus, Experimental , Disease Models, Animal , Drug CombinationsABSTRACT
ABSTRACT PURPOSE: To evaluate the usefulness of a knee osteoarthritis model through functional, radiological and microscopic changes of the synovial membrane. METHODS: Forty eight rats were divided randomly into two groups. The first received 0.9% saline in the joint and corresponded to the control group. The second was submitted to experimental osteoarthritis of the right knee induced by monosodium iodoacetate and corresponded to the osteoarthritis group. All animals were subjected to comparative tests of forced ambulation and joint movements, inability to articulate and tactile allodynia on day 1 post-experiment by forced ambulation (Roto-rod test), joint assessment of disability (weight bearing test) and assessment of tactile allodynia (Von Frey test). After inflammatory induction they were divided into four sub-groups corresponding to the scheduled death in 7, 14, 21 and 28 days when they were submitted to radiographic examination of the knee, arthrotomy and collection of the synovial membrane. RESULTS: The osteoarthritis group showed significant differences compared to control group on days 7 and 14 in Roto-rod, in weight bearing and Von Frey tests in all days, and in radiological evaluation. Microscopic examination of the synovial membrane showed abnormalities of inflammatory character at all stages. CONCLUSION: The osteoarthritis induced by intra-articular monosodium iodoacetate in rats knee is a good model to be used in related research, because it provides mensurable changes on joint movements, tactile allodynia, progressive radiological degeneration and microscopic inflammation of the synovial membrane, that represent markers for osteoarthritis evaluation
Subject(s)
Animals , Male , Rats , Synovial Membrane/pathology , Cartilage, Articular/pathology , Osteoarthritis, Knee/chemically induced , Iodoacetic Acid/adverse effects , Knee Joint/physiopathology , Synovial Membrane/diagnostic imaging , Rats, Wistar , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/pathology , Iodoacetic Acid/administration & dosage , Disease Models, Animal , Hyperalgesia/physiopathology , Hyperalgesia/chemically induced , Hyperalgesia/pathology , Injections, Intra-Arterial , Knee Joint/physiology , MovementABSTRACT
To investigate the influence of Commiphora mukul resin [guggul] on the knee articular cartilage of rats in experimental osteoarthritis. To induce osteoarthritis [OA], single intra-articular injection of MIA [1 mg] in the rat knee joints was performed. Histopathological changes in knee joints were observed after two weeks. The beneficial effect of guggul was studied, orally. The early OA characterized by areas of chondrocytes degeneration in the tibial plateaus and femorat condyles. Changes to the subchondral bone and proteog[ycane contents and synoviat cell proliferation, were observed. Administration of guggul prevented the negative effects of iodoacetate, dose dependently. Chondrocyte damages were significantly prevented and proteoglycane were less affected, especially in high guggul dose and no cell proliferation and inflammatory cell were detected in synovial. The effectiveness of guggut in improvement of histopathotogical damages is emphasized and its chondroprotective effect in vivo is highlighted
Subject(s)
Plant Extracts , Osteoarthritis, Knee/chemically induced , Osteoarthritis, Knee/therapy , Rats , Knee Joint , Cartilage, Articular , Iodoacetates , Injections, Intra-Arterial , Chondrocytes , ProteoglycansABSTRACT
Avaliou-se o efeito da reconstrução do ligamento cruzado cranial, associado ou não ao sulfato de condroitina, na evolução da osteoartrite induzida experimentalmente em cães. Vinte cães hígidos, sem raça definida, machos e fêmeas, com peso corpóreo entre 19 e 25kg, foram submetidos à desmotomia do ligamento cruzado cranial. Trinta dias após, foram separados em dois grupos de 10 animais. Um grupo foi submetido à reconstrução do ligamento cruzado com uso de aloenxerto de ligamento patelar congelado, o outro não. Trinta e um dias após a desmotomia, cada grupo foi dividido em dois subgrupos de cinco animais. Um recebeu sulfato de condroitina, o outro não. Os cães foram avaliados clínica e radiograficamente antes da desmotomia e aos 30, 60 e 90 dias após a desmotomia. No último momento foram realizados exames macro e microscópico. Nos cães submetidos somente à desmotomia e tratados com sulfato de condroitina houve redução na progressão das alterações ósseas, ao exame radiográfico. A reconstrução do ligamento cruzado cranial melhorou a função do membro e, quando associada ao sulfato de condroitina, houve melhor resposta. Não houve diferença entre os subgrupos quanto aos exames macro e microscópico.